The proposed research will investigate cellular immunity in the inflammatory bowel diseases ulcerative colitis and regional enteritis (IBD). Using bacterial extracts and colon tissue components as antigens, several in vitro correlates of cellular immunity will be utilized to examine differences in reactivity among the lymphocytes of IBD patients, patients with other intestinal diseases, and healthy volunteers. The techniques of inhibition of macrophage migration, inhibition of leukocyte migration, and a modified technique of lymphocyte transformation will be used to assess the responses of IBD lymphocytes to the particularly suspect enterobacterial common antigen of Kunin (ECA), such responses representing potential links between normal and abnormal (autoimmune) cellular immunity. Differences in the serum content of factors capable of modulating cellular immune responses, such as certain electrophoretically alpha- migrating glycoproteins and IgA immunoglobulin will be sought between patients and controls. Chemical and immunochemical characterization of these substances will be made. Studies of the chemical nature of migration inhibitory factor (MIF) elaborated by IBD lymphocytes will be made to provide evidence for or against the hypothesis that the IBD lymphocyte may undergo maximum in vivo stimulation of MIF production by ECA or other antigens. In addition, organ culture of colonic tissue will be utilized to (a) demonstrate lymphocyte-mediated tissue damage at the local level, and (b) demonstrate intestinal synthesis of immunoregulatory proteins using the techniques of radioimmunoelectrophoresis and radioimmunodiffusion. Knowledge thus gained concerning the nature of autoimmune events in IBD may permit new therapeutic modes to evolve.